# Ventral Pallidum Circuits in Motivation, Risky Decision Making, and Opioid Addiction

> **NIH NIH K00** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $86,504

## Abstract

Project Summary
Substance use disorder poses a major health threat that costs billions of dollars and thousands of lives
annually, and which is especially acute right now for opioid drugs and cocaine. In susceptible individuals, drugs
of abuse hijack brain circuits that govern motivation and decision making, leading to continued seeking of
drugs despite harmful consequences of using them. Even when people decide to cease their increasingly
maladaptive drug use, in most cases they end up relapsing. In order to help those trying to quit using drugs to
stay abstinent, we must understand how underlying neural circuits of motivation and decision making work in
the brain, and for this we need translationally-relevant animal models. Here, I employ such models, coupled
with cell-type and pathway-specific chemogenetic (DREADD) manipulation approaches to understand how
they process decision making about cocaine and an opioid fentanyl analogue, as well as for natural rewards. I
focus on the role of ventral pallidum (VP) circuits in addiction-relevant behaviors. To date, I have shown that
VP neurons are Fos activated by cocaine-relapse-inducing cues, and that chemogenetic VP inhibition
diminishes relapse-like behavior following voluntary abstinence, especially in the most compulsively cocaine-
seeking individuals (Aim 1.1) I also showed that selective chemogenetic inhibition of VP GABA-expressing
neurons attenuates risky decision making behavior in pursuit of palatable food, and decreases instrumental
responding both in pursuit of valuable foods, and in avoidance of being shocked, indicating a fundamental role
for these neurons in motivation regardless of valence (Aim 1.2). The F99 phase of this award will shift my focus
to an ongoing health crisis: the opioid epidemic. I first confirm my preliminary finding of VP GABA neuron
involvement in relapse to opioid seeking, using a new punishment-induced abstinence relapse procedure that
models human relapse after voluntary abstinence (Aim 2.1). Aim 2.2 addresses the wider circuits in which VP
is embedded to regulate addiction-related motivation. Specifically, we use a pathway-specific DREADD
inhibition approach to test whether VP GABA projections to VTA in particular are involved in opioid addiction.
The proposed training will facilitate my transition to a competitive postdoctoral position focused on in vivo
circuit monitoring, which will dovetail with my expertise in addiction behavioral models, and chemogenetic
circuit manipulations. Through establishment of the Irvine Center for Addiction Neuroscience, UCI offers a
stimulating, collaborative research environment with faculty dedicated to solving the problem of addiction at the
multiple levels with a host of technical resources, mentorship training opportunities, and professional
development workshops. In sum, the F99/K00 will be invaluable for keeping me on a track to tenure and
beyond as an addiction behavioral neuroscientist.

## Key facts

- **NIH application ID:** 10619238
- **Project number:** 8K00DA058260-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Mitchell Farrell
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $86,504
- **Award type:** 8
- **Project period:** 2020-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10619238

## Citation

> US National Institutes of Health, RePORTER application 10619238, Ventral Pallidum Circuits in Motivation, Risky Decision Making, and Opioid Addiction (8K00DA058260-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10619238. Licensed CC0.

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